Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial
Authors: Isla S Mackenzie, Christopher J Hawkey, Ian Ford, Nicola Greenlaw, Filippo Pigazzani, Amy Rogers, Allan D Struthers, Alan G Begg, Li Wei, Anthony J Avery, Jaspal S Taggar, Andrew Walker, Suzanne L Duce, Rebecca J Barr, Jennifer S Dumbleton, Evelien D Rooke, Jonathan N Townend, Lewis D Ritchie, Thomas M MacDonald, Husnat Ahmed, Peter Arthur, Jane Aziz, Lawrence Barnes, Sarah Boyle, Tom Brighton, Morris Brown, Mark Caulfield, Jesse Dawson, Martin Denvir, Alexander SF Doney, Sagar Doshi, Moira Dryburgh, Michael Eddleston, Jim Finlayson, Ahmet Fuat, Jacqueline Furnace, JW Kerr Grieve, Greg Guthrie, Sharon Ham, Emma Isaard, Claudine Jennings, Richard Johnson, Claire Kerr, Sohail Khan, Kailash Krishnan, Susan Long, Anne Mackintosh, Mary Joan Macleod, Terry McCormack, Paul McEleny, Monique Morar, Adnan Nadir, David Newby, Colin Petrie, David Preiss, Stuart Ralston, Marc Randall, Helen Routledge, Saad Shakir, Raj Sharma, Bridget Shepherd, Don Sims, Gordon Snedden, Jasper Trevelyan, Christopher Weir, Robin Weir, Kirsty Wetherall, Robbie Wilson, Adam Wilson, Kris Zutis
Journal: The Lancet (2022)

Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease.ALL-HEART was a multicentre, prospective, randomised, open-label, blinded-endpoint trial done in 18 regional centres in England and Scotland, with patients recruited from 424 primary care practices. Eligible patients were aged 60 years or older, with ischaemic heart disease but no history of gout. Participants were randomly assigned (1:1), using a central web-based randomisation system accessed via a web-based application or an interactive voice response system, to receive oral allopurinol up-titrated to a dose of 600 mg daily (300 mg daily in participants with moderate renal impairment at baseline) or to continue usual care. The primary outcome was the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. The hazard ratio (allopurinol vs usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis (excluding randomly assigned patients later found to have met one of the exclusion criteria). The safety analysis population included all patients in the modified intention-to-treat usual care group and those who took at least one dose of randomised medication in the allopurinol group. This study is registered with the EU Clinical Trials Register, EudraCT 2013-003559-39, and ISRCTN, ISRCTN32017426.Between Feb 7, 2014, and Oct 2, 2017, 5937 participants were enrolled and then randomly assigned to receive allopurinol or usual care. After exclusion of 216 patients after randomisation, 5721 participants (mean age 72·0 years [SD 6·8], 4321 [75·5%] males, and 5676 [99·2%] white) were included in the modified intention-to-treat population, with 2853 in the allopurinol group and 2868 in the usual care group. Mean follow-up time in the study was 4·8 years (1·5). There was no evidence of a difference between the randomised treatment groups in the rates of the primary endpoint. 314 (11·0%) participants in the allopurinol group (2·47 events per 100 patient-years) and 325 (11·3%) in the usual care group (2·37 events per 100 patient-years) had a primary endpoint (hazard ratio [HR] 1·04 [95% CI 0·89-1·21], p=0·65). 288 (10·1%) participants in the allopurinol group and 303 (10·6%) participants in the usual care group died from any cause (HR 1·02 [95% CI 0·87-1·20], p=0·77).In this large, randomised clinical trial in patients aged 60 years or older with ischaemic heart disease but no history of gout, there was no difference in the primary outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death between participants randomised to allopurinol therapy and those randomised to usual care.UK National Institute for Health and Care Research.